Since 1996, the Neuropathology Core (NPC) of the Boston University Alzheimer's Disease Center (BU ADC) has conducted cutting-edge research on the neuropathology of Alzheimer's disease (AD). Recently, the NPC directed groundbreaking research on chronic traumatic encephalopathy (CTE), research that revolutionized public health by identifying repetitive brain trauma as a major risk factor for neurodegeneration, including CTE (6-27). During the last funding cycle, the NPC published preliminary criteria for the neuropathological diagnosis of CTE (9), criteria that are in the process of being validated by a NINDS funded UO1 panel of expert neuropathologists from other ADRCs and academic centers and will eventually be incorporated into NIA-AA guidelines (27). One of the major outcomes from NPC research has been the recognition that some of the clinical symptoms of CTE can be very similar to AD, raising the possibility that some subjects clinically diagnosed with AD dementia may, in fact, have CTE. Our studies have also found beta amyloid (A) deposition in 52% of individuals diagnosed pathologically with CTE (17) and that the presence of A in CTE is significantly associated with increased clinical severity and tau and alpha-synuclein pathology. Ongoing research also indicates that changes of CTE are a common co-morbidity in ADC and other neurodegenerative disease brain banks (26). These advances suggest a dynamic synergism between CTE and AD pathobiology, and highlight the importance of studying the effects of repetitive brain trauma on the development of AD. The overarching goals of the NPC are to conduct and foster research on AD and to determine the relationship of AD and other neurodegenerative pathology to repetitive head impacts (RHI) and CTE. The specific aims of the NPC consist of fundamental Core functions, namely to perform state-of-the-art diagnostic neuropathology, optimally store and distribute CNS tissue and other biospecimens, and provide neuropathological data to the other cores of the BU ADC and to NACC. The specific aims also build upon the significant innovations of the NPC with regard to CTE and focus on determining the relationship of RHI to AD and CTE. Over the past cycle, there have been substantial increases in funding and personnel, including 2 new MD, PhD neuropathologists, as well as large increases in infrastructure and equipment. These expansions have stimulated major technical innovations in qualitative and quantitative neuropathology. Other advances of the NPC include developing biomarkers for AD, CTE and related disorders, expanding the collection of CNS tissue to include spinal cord, eyes, plasma, serum and CSF, and increased collection of control tissues. To accomplish these aims, the NPC will continue to work in close collaboration with the other BU ADC Cores, other ADCs and ADRCs.